Immunotherapy Is Changing Cancer Treatment Forever

I think immunotherapy is great and going to save many lives, but there are still some things that need to be worked out before it's perfect.

Nearing the end of life for a family member

Yeah. I'm dying of a squamous cell carcinoma infestation: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce... and the most recent clinical trial drug that was working, has stopped working: https://jakeseliger.com/2024/05/20/in-which-the-antibody-dru....

One of the options for a next trial is from TScan, "A Basket Study of Customized Autologous TCR-T Cell Therapies." https://www.clinicaltrials.gov/study/NCT05973487?term=tscan0.... On the one hand, it looks very promising; on the other hand, lots of promising treatments fail during dose-escalation, first-in-human trials. To my knowledge, the first humans dosed with TScan's TCR-T therapy got it a few months ago.

I got lucky, too, in that a slot for BGB-A3055 with Tislelizumab, an immunotherapy drug and trial, opened up at NEXT Oncology-Dallas: https://clinicaltrials.gov/study/NCT05935098?term=BGB-A3055&.... One challenge, however, is that I received a bispecific antibody called petosemtamab from Sept 2023 to March 2024, then PDL1V (an antibody drug conjugate), and they're considered immunotherapies, so there's a question of whether continuing to pursue immunotherapies makes sense. By now the number of lines of therapy I've gotten make me ineligible for some trials: https://bessstillman.substack.com/p/the-drugs-killing-dying-..., and I've also blown through the more promising drugs for what is a difficult-to-treat cancer type.

It took just five years to get from their first promising results to FDA approval

This sentence is insane. "Just?" It should be happening in months, not years. These are people with fatal diagnoses. Having the FDA hold up therapies like this is criminal.

At this point the best we are hoping for is a few more years but understand if it doesn't work out. It is still wild to see where we are going. While I am skeptical of many technological claims that get thrown around nowadays, medical advances are still plodding along wonderfully. Even if at times it can be two steps forward, one step back.

It's quite expensive and doesn't always work. We have predictors of whether it works well or not, but nothing has stuck. It's very hard because cancer is hard and immune system is hard, and this is both.

THis whole thing about "immunotherapy is new and has bugs to figure out" is half true, but hell, if "bugs" mean that it doesn't work, the whole reason immunotherapy exists is because the things that came before also had these "bugs" ie people dying.

Every cancer is different. Every cancer is different in every different person. THere are common trends, common genes, common themes, absolutely, but every cancer is different just like every person every face is different. At best you can get a common drug targeting common genes and common themes, just like you could target people with brown hair, but if you happened to have blonde hair you're out of luck until they cook up a solution for that. This is the nature of cancer and where there is no universal cure.

also this board is pretty dang comp sci heavy, and comp sci and physics the instinct is 1000% dunning kruger within the realm of biology or other extraneous inferior-appearing fields. BIology is the most rabbit hole ridden field. The rabbit holes have rabbit holes, and they have their own rabbit holes. You're thinking about cancer but maybe it relates to some evolutionary resistance that was necessary 200 million years ago, and that relates to a biochemical pathway protein binding side. It's a polymath's wet dream really. So it's important not to hand wave or give airs of understanding it. I've been specializing in the area for many years and I can say that nobody understands it really, other than that it works sometimes with some various correlates of when it works. Like most parts of bio, people will specialize in one compenent of the system or one pathway, not the system as a whole. People who claim to capture the system as a whole kinda do interesting things but they don't have the detailed big picture, more like various correlates that are frought with confounders

seems like it's almost the same methodology in making the immune system target specific proteins.

You'd be surprised at the number of cancer treatment studies that are deeply flawed:

- Positive effects may have a low confidence due to small sample size, the joke is that if you can fit the laser pointer between the lines it's considered a success. Cancer is a very tough disease and sometimes positive results are due to noise in the dataset.

- Some studies don't consider overall survival (important because you might not die of cancer but you might die sooner from a side effect like Parkinson's caused by the treatment). See mammograms and colonoscopies for treatments that look like they are almost entirely ineffective.

- Don't compare against the standard of care (its easier to show positive results if you aren't using the best treatments available)

- Allow for self selection (the treatment isn't blind or double blind and people drop out of the control group, skewing the results)

Imo he's an excellent source of the latest data driven results related to cancer and other treatments.